H. Leighton Grimes , PhD

I have a broad background in hematopoiesis, molecular biology, and molecular oncology including mouse modeling of hematopoiesis, myelopoiesis, marrow failure syndromes and leukemia. I received a PhD in Molecular Pathology and Immunology studying gene regulation with Maureen Goodenow (then at University of Florida), then joined Philip Tsichlis (then at Fox Chase Cancer Center) at the time the lab was cloning novel genes activated by Moloney murine leukemia virus insertion mutagenesis (e.g. Akt, Tpl2). I participated in the identification of the Growth factor independent-1 (Gfi1) transcription factor, its DNA binding specificity, named the “SNAG” transcription repressor domain, and genetically linked this domain to Gfi1-directed biology.  My laboratory continues to focus on transcriptional integration of normal and malignant hematopoiesis.  With Marshall Horwitz (U. Wash) we identified humans with mutations in GFI1, who display severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). 

Recently, I collaborated with Jose Cancelas (CCHMC) and Carolyn Lutzko (CCHMC) to generate iPSC from SCN patients, and to clearly demonstrate the role of mutant-neutrophil elastase in the pathogenesis of SCN.  We are currently focused upon dissecting the transcriptional and epigenetic programming engendered by both normal and SCN-mutant Gfi1. To this end we have generated deep single cell RNA Seq (scRNA Seq) data sets from bone marrow stem/progenitor cells, and have collaborated with Nathan Salomonis (CCHMC) to develop Iterative Clustering and Guide Gene Selection (ICGS), a novel bioinformatics tool for unsupervised scRNA Seq analysis. ICGS is capable of identifying key genes within the data sets, elaborating clusters correlated to these genes, and then ordering cells.  In Nature, we (Grimes, Salomonis and Harinder Singh) recently completed a study dissecting homeostatic myeloid development to resolve deep molecular insight into the process of differentiation.  In Cancer Discovery, we recently demonstrated a rapid, fully penetrant model of cytogenetically normal AML, and performed scRNA Seq and ICGS to dissect AML clonality.  By mapping the AML data onto the normal hematopoietic scRNA Seq data we were able to rapidly identify the clonal AML population and uncover leukemia-stem-cell transcriptional programming. Thus, the ICGS algorithm and our deep scRNA Seq data sets facilitate deep mechanistic insight into biological questions.

Peer Reviewed Publications

Velu, Chinavenmeni S; Chaubey, Aditya; Phelan, James D; Horman, Shane R; Wunderlich, Mark; Guzman, Monica L; Jegga, Anil G; Zeleznik-Le, Nancy J; Chen, Jianjun; Mulloy, James C; Cancelas, Jose A; Jordan, Craig T; Aronow, Bruce J; Marcucci, Guido; Bhat, Balkrishen; Gebelein, Brian; Grimes, H Leighton (2014. ) Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity.The Journal of clinical investigation, , 124 (1 ) ,222-36 More Information

Khandanpour, Cyrus; Phelan, James D; Vassen, Lothar; Schütte, Judith; Chen, Riyan; Horman, Shane R; Gaudreau, Marie-Claude; Krongold, Joseph; Zhu, Jinfang; Paul, William E; Dührsen, Ulrich; Göttgens, Bertie; Grimes, H Leighton; Möröy, Tarik (2013. ) Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia.Cancer cell, , 23 (2 ) ,200-14 More Information

Phelan, James D; Saba, Ingrid; Zeng, Hui; Kosan, Christian; Messer, Malynda S; Olsson, H Andre; Fraszczak, Jennifer; Hildeman, David A; Aronow, Bruce J; Möröy, Tarik; Grimes, H Leighton (2013. ) Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors.PLoS genetics, , 9 (9 ) ,e1003713 More Information

Meyer, Sara E; Hasenstein, Jason R; Baktula, Avinash; Velu, Chinavenmani S; Xu, Yan; Wan, Huajing; Whitsett, Jeffrey A; Gilks, C Blake; Grimes, H Leighton (2010. ) Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival.The American journal of pathology, , 177 (3 ) ,1503-13 More Information

Phelan, James D; Shroyer, Noah F; Cook, Tiffany; Gebelein, Brian; Grimes, H Leighton (2010. ) Gfi1-cells and circuits: unraveling transcriptional networks of development and disease.Current opinion in hematology, , 17 (4 ) ,300-7 More Information

Dwivedi, Pankaj; Chutipongtanate, Somchai; Muench, David E; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D (2020. ) SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling.Proteomics. Clinical applications, , e1900144 More Information

Hinge, Ashwini; He, Jingyi; Bartram, James; Javier, Jose; Xu, Juying; Fjellman, Ellen; Sesaki, Hiromi; Li, Tingyu; Yu, Jie; Wunderlich, Mark; Mulloy, James; Kofron, Matthew; Salomonis, Nathan; Grimes, H Leighton; Filippi, Marie-Dominique (2020. ) Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition.Cell stem cell, , 26 (3 ) ,420-430.e6 More Information

Yue, Lanzhu; Sharma, Vasundhara; Horvat, Nathan P; Akuffo, Afua A; Beatty, Matthew S; Murdun, Cem; Colin, Christelle; Billington, Julia M R; Goodheart, William E; Sahakian, Eva; Zhang, Ling; Powers, John J; Amin, Narmin E; Lambert-Showers, Que T; Darville, Lancia N; Pinilla-Ibarz, Javier; Reuther, Gary W; Wright, Kenneth L; Conti, Chiara; Lee, Jennifer Y; Zheng, Xiaozhang; Ng, Pui Yee; Martin, Matthew W; Marshall, C Gary; Koomen, John M; Levine, Ross L; Verma, Amit; Grimes, H Leighton; Sotomayor, Eduardo M; Shao, Zonghong; Epling-Burnette, Pearlie K (2020. ) HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms.Blood, , 135 (3 ) ,191-207 More Information

Lucas, Daniel; Salomonis, Nathan; Grimes, H Leighton (2020. ) Unraveling bone marrow architecture.Nature cell biology, , 22 (1 ) ,5-6 More Information

Horman, Shane R; Velu, Chinavenmeni S; Chaubey, Aditya; Bourdeau, Tristan; Zhu, Jinfang; Paul, William E; Gebelein, Brian; Grimes, H Leighton (2009. ) Gfi1 integrates progenitor versus granulocytic transcriptional programming.Blood, , 113 (22 ) ,5466-75 More Information

DePasquale, Erica A K; Schnell, Daniel; Dexheimer, Phillip; Ferchen, Kyle; Hay, Stuart; Chetal, Kashish; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Salomonis, Nathan (2019. ) cellHarmony: cell-level matching and holistic comparison of single-cell transcriptomes.Nucleic acids research, , 47 (21 ) ,e138 More Information

Velu, Chinavenmeni S; Baktula, Avinash M; Grimes, H Leighton (2009. ) Gfi1 regulates miR-21 and miR-196b to control myelopoiesis.Blood, , 113 (19 ) ,4720-8 More Information

DePasquale, Erica A K; Schnell, Daniel J; Van Camp, Pieter-Jan; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Singh, Harinder; Salomonis, Nathan (2019. ) DoubletDecon: Deconvoluting Doublets from Single-Cell RNA-Sequencing Data.Cell reports, , 29 (6 ) ,1718-1727.e8 More Information

Gu, YuanYuan; Harley, Isaac T W; Henderson, Lindsay B; Aronow, Bruce J; Vietor, Ilja; Huber, Lukas A; Harley, John B; Kilpatrick, Jeffrey R; Langefeld, Carl D; Williams, Adrienne H; Jegga, Anil G; Chen, Jing; Wills-Karp, Marsha; Arshad, S Hasan; Ewart, Susan L; Thio, Chloe L; Flick, Leah M; Filippi, Marie-Dominique; Grimes, H Leighton; Drumm, Mitchell L; Cutting, Garry R; Knowles, Michael R; Karp, Christopher L (2009. ) Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease.Nature, , 458 (7241 ) ,1039-42 More Information

Adelman, Emmalee R; Huang, Hsuan-Ting; Roisman, Alejandro; Olsson, André; Colaprico, Antonio; Qin, Tingting; Lindsley, R Coleman; Bejar, Rafael; Salomonis, Nathan; Grimes, H Leighton; Figueroa, Maria E (2019. ) Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.Cancer discovery, , 9 (8 ) ,1080-1101 More Information

Duy, Cihangir; Teater, Matt; Garrett-Bakelman, Francine E; Lee, Tak C; Meydan, Cem; Glass, Jacob L; Li, Meng; Hellmuth, Johannes C; Mohammad, Helai P; Smitheman, Kimberly N; Shih, Alan H; Abdel-Wahab, Omar; Tallman, Martin S; Guzman, Monica L; Muench, David; Grimes, H Leighton; Roboz, Gail J; Kruger, Ryan G; Creasy, Caretha L; Paietta, Elisabeth M; Levine, Ross L; Carroll, Martin; Melnick, Ari M (2019. ) Rational Targeting of Cooperating Layers of the Epigenome Yields Enhanced Therapeutic Efficacy against AML.Cancer discovery, , 9 (7 ) ,872-889 More Information

Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Virendra K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton (2019. ) Author Correction: Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.Nature, , 569 (7755 ) ,E3 More Information

Li-Kroeger, David; Witt, Lorraine M; Grimes, H Leighton; Cook, Tiffany A; Gebelein, Brian (2008. ) Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS.Developmental cell, , 15 (2 ) ,298-308 More Information

Park, Derek S; Akuffo, Afua A; Muench, David E; Grimes, H Leighton; Epling-Burnette, Pearlie K; Maini, Philip K; Anderson, Alexander R A; Bonsall, Michael B (2019. ) Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation.PLoS computational biology, , 15 (4 ) ,e1006913 More Information

Zarebski, Adrian; Velu, Chinavenmeni S; Baktula, Avinash M; Bourdeau, Tristan; Horman, Shane R; Basu, Sudeep; Bertolone, Salvatore J; Horwitz, Marshal; Hildeman, David A; Trent, John O; Grimes, H Leighton (2008. ) Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1.Immunity, , 28 (3 ) ,370-80 More Information

Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D (2019. ) Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors.Scientific data, , 6 (1 ) ,21 More Information

Lee, Catherine; Rudneva, Vasilisa A; Erkek, Serap; Zapatka, Marc; Chau, Lianne Q; Tacheva-Grigorova, Silvia K; Garancher, Alexandra; Rusert, Jessica M; Aksoy, Ozlem; Lea, Robin; Mohammad, Helai P; Wang, Jianxun; Weiss, William A; Grimes, H Leighton; Pfister, Stefan M; Northcott, Paul A; Wechsler-Reya, Robert J (2019. ) Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.Nature communications, , 10 (1 ) ,332 More Information

Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D (2019. ) Time resolved quantitative phospho-tyrosine analysis reveals Bruton's Tyrosine kinase mediated signaling downstream of the mutated granulocyte-colony stimulating factor receptors.Leukemia, , 33 (1 ) ,75-87 More Information

Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S (2018. ) The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.Cell reports, , 25 (11 ) ,3229 More Information

Kazanjian, Avedis; Gross, Eleanore A; Grimes, H Leighton (2006. ) The growth factor independence-1 transcription factor: new functions and new insights.Critical reviews in oncology/hematology, , 59 (2 ) ,85-97 More Information

Hay, Stuart B; Ferchen, Kyle; Chetal, Kashish; Grimes, H Leighton; Salomonis, Nathan (2018. ) The Human Cell Atlas bone marrow single-cell interactive web portal.Experimental hematology, , 68 ,51-61 More Information

Muench, David E; Ferchen, Kyle; Velu, Chinavenmeni S; Pradhan, Kith; Chetal, Kashish; Chen, Xiaoting; Weirauch, Matthew T; Colmenares, Clemencia; Verma, Amit; Salomonis, Nathan; Grimes, H Leighton (2018. ) SKI controls MDS-associated chronic TGF-? signaling, aberrant splicing, and stem cell fitness.Blood, , 132 (21 ) ,e24-e34 More Information

Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S (2018. ) The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.Cell reports, , 25 (8 ) ,2083-2093.e4 More Information

Kazanjian, Avedis; Wallis, Deeann; Au, Nicholas; Nigam, Rupesh; Venken, Koen J T; Cagle, Philip T; Dickey, Burton F; Bellen, Hugo J; Gilks, C Blake; Grimes, H Leighton (2004. ) Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells.Cancer research, , 64 (19 ) ,6874-82 More Information

Hayashi, Yoshihiro; Zhang, Yue; Yokota, Asumi; Yan, Xiaomei; Liu, Jinqin; Choi, Kwangmin; Li, Bing; Sashida, Goro; Peng, Yanyan; Xu, Zefeng; Huang, Rui; Zhang, Lulu; Freudiger, George M; Wang, Jingya; Dong, Yunzhu; Zhou, Yile; Wang, Jieyu; Wu, Lingyun; Bu, Jiachen; Chen, Aili; Zhao, Xinghui; Sun, Xiujuan; Chetal, Kashish; Olsson, Andre; Watanabe, Miki; Romick-Rosendale, Lindsey E; Harada, Hironori; Shih, Lee-Yung; Tse, William; Bridges, James P; Caligiuri, Michael A; Huang, Taosheng; Zheng, Yi; Witte, David P; Wang, Qian-Fei; Qu, Cheng-Kui; Salomonis, Nathan; Grimes, H Leighton; Nimer, Stephen D; Xiao, Zhijian; Huang, Gang (2018. ) Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.Cancer discovery, , 8 (11 ) ,1438-1457 More Information

Meyer, Sara E; Muench, David E; Rogers, Andrew M; Newkold, Tess J; Orr, Emily; O'Brien, Eric; Perentesis, John P; Doench, John G; Lal, Ashish; Morris, Patrick J; Thomas, Craig J; Lieberman, Judy; McGlinn, Edwina; Aronow, Bruce J; Salomonis, Nathan; Grimes, H Leighton (2018. ) miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.The Journal of experimental medicine, , 215 (8 ) ,2115-2136 More Information

Zhang, Cuiping; D'Alessandro, Angelo; Wellendorf, Ashley M; Mohmoud, Fatima; Serrano-Lopez, Juana; Perentesis, John P; Komurov, Kakajan; Alexe, Gabriela; Stegmaier, Kimberly; Whitsett, Jeffrey A; Grimes, H Leighton; Cancelas, Jose A (2018. ) KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia.Oncotarget, , 9 (51 ) ,29665-29679 More Information

Park, Jung-Hyun; Yu, Qing; Erman, Batu; Appelbaum, Jacob S; Montoya-Durango, Diego; Grimes, H Leighton; Singer, Alfred (2004. ) Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival.Immunity, , 21 (2 ) ,289-302 More Information

Zhou, Yile; Yan, Xiaomei; Feng, Xiaomin; Bu, Jiachen; Dong, Yunzhu; Lin, Peipei; Hayashi, Yoshihiro; Huang, Rui; Olsson, Andre; Andreassen, Paul R; Grimes, H Leighton; Wang, Qian-Fei; Cheng, Tao; Xiao, Zhijian; Jin, Jie; Huang, Gang (2018. ) Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation.Haematologica, , 103 (7 ) ,1110-1123 More Information

Doan, Loretta L; Porter, Susan D; Duan, Zhijun; Flubacher, Marcella M; Montoya, Diego; Tsichlis, Philip N; Horwitz, Marshall; Gilks, C Blake; Grimes, H Leighton (2004. ) Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells.Nucleic acids research, , 32 (8 ) ,2508-19 More Information

Kleeman, Benjamin; Olsson, Andre; Newkold, Tess; Kofron, Matt; DeLay, Monica; Hildeman, David; Grimes, H Leighton (2018. ) A guide to choosing fluorescent protein combinations for flow cytometric analysis based on spectral overlap.Cytometry. Part A : the journal of the International Society for Analytical Cytology, , 93 (5 ) ,556-562 More Information

Lee, Jung-Mi; Govindarajah, Vinothini; Goddard, Bryan; Hinge, Ashwini; Muench, David E; Filippi, Marie-Dominique; Aronow, Bruce; Cancelas, Jose A; Salomonis, Nathan; Grimes, H Leighton; Reynaud, Damien (2018. ) Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression.The Journal of experimental medicine, , 215 (2 ) ,627-644 More Information

Yáñez, Alberto; Coetzee, Simon G; Olsson, Andre; Muench, David E; Berman, Benjamin P; Hazelett, Dennis J; Salomonis, Nathan; Grimes, H Leighton; Goodridge, Helen S (2017. ) Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.Immunity, , 47 (5 ) ,890-902.e4 More Information

Person, Richard E; Li, Feng-Qian; Duan, Zhijun; Benson, Kathleen F; Wechsler, Jeremy; Papadaki, Helen A; Eliopoulos, George; Kaufman, Christina; Bertolone, Salvatore J; Nakamoto, Betty; Papayannopoulou, Thalia; Grimes, H Leighton; Horwitz, Marshall (2003. ) Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2.Nature genetics, , 34 (3 ) ,308-12 More Information

Fang, Jing; Barker, Brenden; Bolanos, Lyndsey; Liu, Xiaona; Jerez, Andres; Makishima, Hideki; Christie, Susanne; Chen, Xiaoting; Rao, Dinesh S; Grimes, H Leighton; Komurov, Kakajan; Weirauch, Matthew T; Cancelas, Jose A; Maciejewski, Jaroslaw P; Starczynowski, Daniel T (2014. ) Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-?B gene network.Cell reports, , 8 (5 ) ,1328-38 More Information

Doan, Loretta L; Kitay, Mary Kate; Yu, Qing; Singer, Alfred; Herblot, Sabine; Hoang, Trang; Bear, Susan E; Morse, Herbert C; Tsichlis, Philip N; Grimes, H Leighton (2003. ) Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment. Journal of immunology (Baltimore, Md. : 1950), , 170 (5 ) ,2356-66

Northcott, Paul A; Lee, Catherine; Zichner, Thomas; Stütz, Adrian M; Erkek, Serap; Kawauchi, Daisuke; Shih, David J H; Hovestadt, Volker; Zapatka, Marc; Sturm, Dominik; Jones, David T W; Kool, Marcel; Remke, Marc; Cavalli, Florence M G; Zuyderduyn, Scott; Bader, Gary D; VandenBerg, Scott; Esparza, Lourdes Adriana; Ryzhova, Marina; Wang, Wei; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Jäger, Natalie; Buchhalter, Ivo; Imbusch, Charles D; Zipprich, Gideon; Raeder, Benjamin; Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan; Brors, Benedikt; Lawerenz, Chris; Eils, Jürgen; Warnatz, Hans-Jörg; Risch, Thomas; Yaspo, Marie-Laure; Weber, Ursula D; Bartholomae, Cynthia C; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M (2014. ) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.Nature, , 511 (7510 ) ,428-34 More Information

Boespflug, Nicholas D; Kumar, Sachin; McAlees, Jaclyn W; Phelan, James D; Grimes, H Leighton; Hoebe, Kasper; Hai, Tsonwin; Filippi, Marie-Dominique; Karp, Christopher L (2014. ) ATF3 is a novel regulator of mouse neutrophil migration.Blood, , 123 (13 ) ,2084-93 More Information

Yáñez, Alberto; Goodridge, Helen S; Grimes, H Leighton (2017. ) Counting the cost of lineage decisions.Nature immunology, , 18 (8 ) ,872-873 More Information

Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C; Trump, Lisa; Salipante, Stephen J; Cheng, Jerry C; Donadieu, Jean; Glaubach, Taly; Corey, Seth J; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A; Horwitz, Marshall S (2014. ) Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms.Blood, , 123 (4 ) ,562-9 More Information

Kesarwani, Meenu; Kincaid, Zachary; Gomaa, Ahmed; Huber, Erika; Rohrabaugh, Sara; Siddiqui, Zain; Bouso, Muhammad F; Latif, Tahir; Xu, Ming; Komurov, Kakajan; Mulloy, James C; Cancelas, Jose A; Grimes, H Leighton; Azam, Mohammad (2017. ) Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.Nature medicine, , 23 (4 ) ,472-482 More Information

Goyama, Susumu; Schibler, Janet; Cunningham, Lea; Zhang, Yue; Rao, Yalan; Nishimoto, Nahoko; Nakagawa, Masahiro; Olsson, Andre; Wunderlich, Mark; Link, Kevin A; Mizukawa, Benjamin; Grimes, H Leighton; Kurokawa, Mineo; Liu, P Paul; Huang, Gang; Mulloy, James C (2013. ) Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells.The Journal of clinical investigation, , 123 (9 ) ,3876-88 More Information

Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Viren K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton (2016. ) Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.Nature, , 537 (7622 ) ,698-702 More Information

Raines, Anna M; Adam, Mike; Magella, Bliss; Meyer, Sara E; Grimes, H Leighton; Dey, Sudhansu K; Potter, S Steven (2013. ) Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts.Development (Cambridge, England), , 140 (14 ) ,2942-52 More Information

Meyer, Sara E; Qin, Tingting; Muench, David E; Masuda, Kohei; Venkatasubramanian, Meenakshi; Orr, Emily; Suarez, Lauren; Gore, Steven D; Delwel, Ruud; Paietta, Elisabeth; Tallman, Martin S; Fernandez, Hugo; Melnick, Ari; Le Beau, Michelle M; Kogan, Scott; Salomonis, Nathan; Figueroa, Maria E; Grimes, H Leighton (2016. ) DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia.Cancer discovery, , 6 (5 ) ,501-15 More Information

Horwitz, Marshall S; Corey, Seth J; Grimes, H Leighton; Tidwell, Timothy (2013. ) ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology.Hematology/oncology clinics of North America, , 27 (1 ) ,19-41, vii More Information

Muench, David E; Grimes, H Leighton (2015. ) Transcriptional Control of Stem and Progenitor Potential.Current stem cell reports, , 1 (3 ) ,139-150 More Information

Unnisa, Zeenath; Clark, Jason P; Roychoudhury, Jayeeta; Thomas, Elizabeth; Tessarollo, Lino; Copeland, Neal G; Jenkins, Nancy A; Grimes, H Leighton; Kumar, Ashish R (2012. ) Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress.Blood, , 120 (25 ) ,4973-81 More Information

Nayak, Ramesh C; Trump, Lisa R; Aronow, Bruce J; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M; Valencia, C Alexander; Paddison, Patrick J; Horwitz, Marshall S; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A (2015. ) Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells.The Journal of clinical investigation, , 125 (8 ) ,3103-16 More Information

Khandanpour, Cyrus; Krongold, Joseph; Schütte, Judith; Bouwman, Frederique; Vassen, Lothar; Gaudreau, Marie-Claude; Chen, Riyan; Calero-Nieto, Fernando J; Diamanti, Evangelia; Hannah, Rebecca; Meyer, Sara E; Grimes, H Leighton; van der Reijden, Bert A; Jansen, Joop H; Patel, Chandrashekhar V; Peeters, Justine K; Löwenberg, Bob; Dührsen, Ulrich; Göttgens, Bertie; Möröy, Tarik (2012. ) The human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice.Blood, , 120 (19 ) ,4006-17 More Information

Zhang, Yue; Yan, Xiaomei; Sashida, Goro; Zhao, Xinghui; Rao, Yalan; Goyama, Susumu; Whitman, Susan P; Zorko, Nicholas; Bernot, Kelsie; Conway, Rajeana M; Witte, David; Wang, Qian-Fei; Tenen, Daniel G; Xiao, Zhijian; Marcucci, Guido; Mulloy, James C; Grimes, H Leighton; Caligiuri, Michael A; Huang, Gang (2012. ) Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells.Blood, , 120 (5 ) ,1118-29 More Information

Stoffers, Sara L; Meyer, Sara E; Grimes, H Leighton (2012. ) MicroRNAs in the midst of myeloid signal transduction.Journal of cellular physiology, , 227 (2 ) ,525-33 More Information

Velu, Chinavenmeni S; Grimes, H Leighton (2012. ) Utilizing antagomiR (antisense microRNA) to knock down microRNA in murine bone marrow cells.Methods in molecular biology (Clifton, N.J.), , 928 ,185-95 More Information

D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L; Patrene, Kenneth D; Yu, Shibing; Velu, Chinavenmeni S; Xiao, Guozhi; Grimes, H Leighton; Roodman, G David; Galson, Deborah L (2011. ) Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease.Blood, , 118 (26 ) ,6871-80 More Information

McClendon, A Kathleen; Dean, Jeffry L; Ertel, Adam; Fu, Zhiyan; Rivadeneira, Dayana B; Reed, Christopher A; Bourgo, Ryan J; Witkiewicz, Agnieszka; Addya, Sankar; Mayhew, Christopher N; Grimes, H Leighton; Fortina, Paolo; Knudsen, Erik S (2011. ) RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage.Gastroenterology, , 141 (4 ) ,1439-50 More Information

Kurtulus, Sema; Tripathi, Pulak; Moreno-Fernandez, Maria E; Sholl, Allyson; Katz, Jonathan D; Grimes, H Leighton; Hildeman, David A (2011. ) Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim.Journal of immunology (Baltimore, Md. : 1950), , 186 (10 ) ,5729-37 More Information

Guo, Fukun; Zhang, Shuangmin; Tripathi, Pulak; Mattner, Jochen; Phelan, James; Sproles, Alyssa; Mo, Jun; Wills-Karp, Marsha; Grimes, H Leighton; Hildeman, David; Zheng, Yi (2011. ) Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation.PloS one, , 6 (3 ) ,e18002 More Information

Guo, Fukun; Hildeman, David; Tripathi, Pulak; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi (2010. ) Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis.Proceedings of the National Academy of Sciences of the United States of America, , 107 (43 ) ,18505-10 More Information

Tripathi, Pulak; Kurtulus, Sema; Wojciechowski, Sara; Sholl, Allyson; Hoebe, Kasper; Morris, Suzanne C; Finkelman, Fred D; Grimes, H Leighton; Hildeman, David A (2010. ) STAT5 is critical to maintain effector CD8+ T cell responses.Journal of immunology (Baltimore, Md. : 1950), , 185 (4 ) ,2116-24 More Information

Kong, Kimi Y; Owens, Kristin S; Rogers, Jason H; Mullenix, Jason; Velu, Chinavenmeni S; Grimes, H Leighton; Dahl, Richard (2010. ) MIR-23A microRNA cluster inhibits B-cell development.Experimental hematology, , 38 (8 ) ,629-640.e1 More Information

Sharif-Askari, Ehssan; Vassen, Lothar; Kosan, Christian; Khandanpour, Cyrus; Gaudreau, Marie-Claude; Heyd, Florian; Okayama, Taro; Jin, Jianmin; Rojas, Meghan E B; Grimes, H Leighton; Zeng, Hui; Möröy, Tarik (2010. ) Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65.Molecular and cellular biology, , 30 (16 ) ,3929-42 More Information

Barnes, Michael J; Aksoylar, Halil; Krebs, Philippe; Bourdeau, Tristan; Arnold, Carrie N; Xia, Yu; Khovananth, Kevin; Engel, Isaac; Sovath, Sosathya; Lampe, Kristin; Laws, Eleana; Saunders, Amy; Butcher, Geoffrey W; Kronenberg, Mitchell; Steinbrecher, Kris; Hildeman, David; Grimes, H Leighton; Beutler, Bruce; Hoebe, Kasper (2010. ) Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice.Journal of immunology (Baltimore, Md. : 1950), , 184 (7 ) ,3743-54 More Information

Guo, Fukun; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi (2009. ) Rho GTPase Cdc42 is essential for B-lymphocyte development and activation.Blood, , 114 (14 ) ,2909-16 More Information

Arumugam, Paritha I; Urbinati, Fabrizia; Velu, Chinavenmeni S; Higashimoto, Tomoyasu; Grimes, H Leighton; Malik, Punam (2009. ) The 3' region of the chicken hypersensitive site-4 insulator has properties similar to its core and is required for full insulator activity.PloS one, , 4 (9 ) ,e6995 More Information

Salipante, Stephen J; Rojas, Meghan E B; Korkmaz, Brice; Duan, Zhijun; Wechsler, Jeremy; Benson, Kathleen F; Person, Richard E; Grimes, H Leighton; Horwitz, Marshall S (2009. ) Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase.Molecular and cellular biology, , 29 (16 ) ,4394-405 More Information

Popovic, Relja; Riesbeck, Laurie E; Velu, Chinavenmeni S; Chaubey, Aditya; Zhang, Jiwang; Achille, Nicholas J; Erfurth, Frank E; Eaton, Katherine; Lu, Jun; Grimes, H Leighton; Chen, Jianjun; Rowley, Janet D; Zeleznik-Le, Nancy J (2009. ) Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization.Blood, , 113 (14 ) ,3314-22 More Information

Montoya-Durango, Diego E; Velu, Chinavenmeni S; Kazanjian, Avedis; Rojas, Meghan E B; Jay, Chris M; Longmore, Gregory D; Grimes, H Leighton (2008. ) Ajuba functions as a histone deacetylase-dependent co-repressor for autoregulation of the growth factor-independent-1 transcription factor.The Journal of biological chemistry, , 283 (46 ) ,32056-65 More Information

Duan, Zhijun; Person, Richard E; Lee, Hu-Hui; Huang, Shi; Donadieu, Jean; Badolato, Raffaele; Grimes, H Leighton; Papayannopoulou, Thalia; Horwitz, Marshall S (2007. ) Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5.Molecular and cellular biology, , 27 (19 ) ,6889-902 More Information

Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H Leighton; Katz, Jonathan D; Finkelman, Fred D; Hildeman, David A (2007. ) Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis.The Journal of experimental medicine, , 204 (7 ) ,1665-75 More Information

Linnoila, R Ilona; Jensen-Taubman, Sandra; Kazanjian, Avedis; Grimes, H Leighton (2007. ) Loss of GFI1 impairs pulmonary neuroendorine cell proliferation, but the neuroendocrine phenotype has limited impact on post-naphthalene airway repair.Laboratory investigation; a journal of technical methods and pathology, , 87 (4 ) ,336-44 More Information

Duan, Zhijun; Zarebski, Adrian; Montoya-Durango, Diego; Grimes, H Leighton; Horwitz, Marshall (2005. ) Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1.Molecular and cellular biology, , 25 (23 ) ,10338-51 More Information

Dwivedi, Prem P; Anderson, Paul H; Omdahl, John L; Grimes, H Leighton; Morris, Howard A; May, Brian K (2005. ) Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells.Endocrine-related cancer, , 12 (2 ) ,351-65 More Information

Grimes, H Leighton; Schanie, Carrie L; Huang, Yiming; Cramer, Daniel; Rezzoug, Francine; Fugier-Vivier, Isabelle; Ildstad, Suzanne T (2004. ) Graft facilitating cells are derived from hematopoietic stem cells and functionally require CD3, but are distinct from T lymphocytes.Experimental hematology, , 32 (10 ) ,946-54 More Information

Huang, Yiming; Rezzoug, Francine; Chilton, Paula M; Grimes, H Leighton; Cramer, Daniel E; Ildstad, Suzanne T (2004. ) Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment.Blood, , 104 (3 ) ,873-80 More Information

McGhee, Laura; Bryan, Josh; Elliott, Liza; Grimes, H Leighton; Kazanjian, Avedis; Davis, J Nathan; Meyers, Shari (2003. ) Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism.Journal of cellular biochemistry, , 89 (5 ) ,1005-18 More Information

Doan, Loretta L; Tanner, Michael K; Grimes, H Leighton (2003. ) Intranuclear staining of proteins in heterogeneous cell populations and verification of nuclear localization by flow cytometric analysis.Journal of immunological methods, , 279 (1-2 ) ,193-8 More Information

Wallis, Deeann; Hamblen, Melanie; Zhou, Yi; Venken, Koen J T; Schumacher, Armin; Grimes, H Leighton; Zoghbi, Huda Y; Orkin, Stuart H; Bellen, Hugo J (2003. ) The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival.Development (Cambridge, England), , 130 (1 ) ,221-32 More Information

cancer, leukemia, hematopoiesis, blood, bone marrow failure, neutropenia, pediatric oncology, oncogene, models, therapy

Academic - Cincinnati Children's Hospital
Division of Immunobiology
Phone: 513-636-6089
Lee.Grimes@cchmc.org